Extracapsular cataract extraction has recently become a more popular method of removing cataracts, probably because of its lower incidence of post-operative complications in terms of cystoid macular edema and possible retinal detachment. The advent of an improved extracapsular extraction technique such as phacoemulsification and the requirement of an intact posterior lens capsule for implantation of a wide variety of intraocular lenses have certainly played an important role in influencing such a trend. The only possible disadvantage of extracapsular cataract extraction is the high incidence of posterior lens capsule opacification, which requires additional surgical procedures (posterior capsulotomy or repolishing of the posterior lens capsule) to obtain good vision.
The pathogenesis of posterior lens capsule opacification after extracapsular cataract extraction is known: the remnant lens epithelial cells proliferate on the posterior lens capsule to form abortive lens "fibers" and "bladder" cells (i.e. Elschnig's pearls).
As reported in Contact and Intraocular Lens Medical Journal, Vol. 5, No. 4, October/December 1979, pp. 175-178, After-Cataract: Studies of Chemical and Radiation Inhibition, by Roy et al, chemical and radiation means have been attempted to try to find a method associated with extracapsular cataract surgery which would lower the incident of after cataract growth. As reported in this publication the chemicals used (vincristine and vinblastine) were tried to chemically inhibit subcapsular epithelial cells because they had been found to have a direct inhibitory effect on cell mitotis (Goodman, L. S., and Gillman, A: The Pharmacological Basis of Therapeutics, Maximilan, New York, 1965, pp. 1373-1376). Vincristine and vinblastine were found to inhibit the corneal wound so that it healed poorly, and because of the deletory effects to the cornea and iris it was the opinion of the authors that these drugs should not be used in further animal studies to try to inhibit subcapsular epithelial proliferation. The authors further stated that radiation given the second day after surgery appeared to be the most effective of all dosage schedules, however, they indicate that there is some danger of injury, the authors concluding that it is difficult to say, however, that if one used radiation in humans whether there would be problems or not.
The authors further pointed out that if there were a drug or chemical system that could be found which would inhibit selectively the subcapsular epithelial cells, this might be a useful way to help prevent after cataracts.
Applicants are aware of the instillation of the mitotic inhibitors methotrexate and retinoic acid, or mixtures thereof, in the anterior chamber of the eye in minimal effective dosages at the end of one lens epithelial cell cycle, which instillation effectively prevents posterior lens capsule opacification without ocular compromise after extracapsular cataract extraction.
Methotrexate is a cycle-dependent anti-metabolite which inhibits the enzyme dihydrofolate reductase and thus interferes with the maintenance of intracellular pool of reduced folates.
Retinoic acid, the exact mechanism being unknown, appears to inhibit either cellular division or DNA synthesis or both.
The present invention constitutes an improvement by producing and the use of monoclonal antibodies specific to residual lens epithelial cells which can be used to destroy these cells selectively without damage to other parts of the eye at the time of the original cataract removal.